DESCRIPTION (Adapted from applicant's abstract and specific aims): The normal lung macrophage shows a desirable "down-regulation" of proinflammatory response when encountering unopsonized inert environmental particles, allowing clearance of such particles without lung injury. The basis for this lung-protective down-regulation or how it is overcome during pulmonary inflammation is poorly understood. The central hypothesis is that a constitutively expressed type III NOS functions in normal AMs to down-regulate activation responses to unopsonized phagocytosis, primarily through NO-mediated inhibition of mitochondrial respiration needed for effective redox-based activation signaling. The specific aims are to: 1) characterize the expression of NOS-III in normal and activated AMs; and 2) characterize the function of NOS-III in modulating AM response to inhaled particles.